Use of neurokinin-1 antagonists to treat a variety of pruritic conditions

Abstract

The disclosure relates to the use of neurokinin-1 (NK-1) antagonists, such as serlopitant, in treating acute or chronic pruritus associated with a variety of medical conditions, including dermatitis/eczema, psoriasis, prurigo, urticaria, cutaneous T-cell lymphoma, epidermolysis bullosa, bums and hepato-biliary diseases, or/and treating the medical conditions themselves. One or more additional antipruritic or therapeutic agents can optionally be used in combination with an NK-1 antagonist to treat acute or chronic pruritus associated with a medical condition or/and the medical condition itself.

What is claimed is: 
     
         1 . A method of treating pruritus associated with dermatitis/eczema, psoriasis, prurigo, urticaria, cutaneous T-cell lymphoma, epidermolysis bullosa, a burn or a hepato-biliary disease, comprising administering to a subject in need of treatment a therapeutically effective amount of a neurokinin-1 (NK-1) antagonist selected from aprepitant, fosaprepitant, netupitant, orvepitant, rolapitant, tradipitant, vestipitant, DNK-333, SCH-900978, and pharmaceutically acceptable salts thereof, wherein:
 the NK-1 antagonist is not aprepitant for the treatment of pruritus associated with atopic dermatitis or prurigo nodularis;   the NK-1 antagonist is not orvepitant for the treatment of pruritus associated with a burn; and   the NK-1 antagonist is not tradipitant for the treatment of pruritus associated with atopic dermatitis.   
     
     
         2 . A method of treating pruritus associated with dermatitis/eczema, psoriasis, prurigo, urticaria, cutaneous T-cell lymphoma, epidermolysis bullosa, a burn or a hepato-biliary disease, comprising administering to a subject in need of treatment a therapeutically effective amount of a neurokinin-1 (NK-1) antagonist and a therapeutically effective amount of an H 4  antihistamine. 
     
     
         3 . The method of  claim 2 , wherein the NK-1 antagonist is selected from aprepitant, fosaprepitant, befetupitant, casopitant, dapitant, ezlopitant, lanepitant, maropitant, netupitant, nolpitantium, orvepitant, rolapitant, serlopitant, tradipitant, vestipitant, vofopitant, hydroxyphenyl propamidobenzoic acid, maltooligosaccharides (e.g., maltotetraose and maltopentaose), spantides (e.g., spantide I and II), AV-608, AV-818, AZD-2624, BIT 1149 CL, CGP-49823, CJ-17493, CP-96345, CP-99994, CP-122721, DNK-333, FK-224, FK-888, GR-205171, GSK-424887, HSP-117, KRP-103, L-703606, L-733060, L-736281, L-759274, L-760735, LY-686017, M516102, MDL-105212, NKP-608, R-116031, R-116301, RP-67580, SCH-206272, SCH-388714, SCH-900978, SLV-317, SSR-240600, T-2328, TA-5538, TAK-637, TKA-731, ZD-4974, ZD-6021, and pharmaceutically acceptable salts thereof. 
     
     
         4 . The method of  claim 2  or  3 , wherein the NK-1 antagonist is serlopitant or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The method of any one of  claims 2  to  4 , wherein the H 4  antihistamine is selected from clobenpropit, thioperamide, A943931, A987306, JNJ-7777120, VUF-6002, ZPL-389, and pharmaceutically acceptable salts thereof. 
     
     
         6 . The method of  claim 5 , wherein the H 4  antihistamine is ZPL-389 or a pharmaceutically acceptable salt thereof. 
     
     
         7 . The method of any one of  claims 2  to  6 , wherein the pruritus is associated with dermatitis/eczema (e.g., atopic dermatitis) or psoriasis (e.g., plaque psoriasis). 
     
     
         8 . A method of treating pruritus associated with dermatitis/eczema, psoriasis, prurigo, urticaria, cutaneous T-cell lymphoma, epidermolysis bullosa, a burn or a hepato-biliary disease, comprising administering to a subject in need of treatment a therapeutically effective amount of a neurokinin-1 (NK-1) antagonist and a therapeutically effective amount of a kappa-opioid receptor agonist. 
     
     
         9 . The method of  claim 8 , wherein the NK-1 antagonist is selected from aprepitant, fosaprepitant, befetupitant, casopitant, dapitant, ezlopitant, lanepitant, maropitant, netupitant, nolpitantium, orvepitant, rolapitant, serlopitant, tradipitant, vestipitant, vofopitant, hydroxyphenyl propamidobenzoic acid, maltooligosaccharides (e.g., maltotetraose and maltopentaose), spantides (e.g., spantide I and II), AV-608, AV-818, AZD-2624, BIT 1149 CL, CGP-49823, CJ-17493, CP-96345, CP-99994, CP-122721, DNK-333, FK-224, FK-888, GR-205171, GSK-424887, HSP-117, KRP-103, L-703606, L-733060, L-736281, L-759274, L-760735, LY-686017, M516102, MDL-105212, NKP-608, R-116031, R-116301, RP-67580, SCH-206272, SCH-388714, SCH-900978, SLV-317, SSR-240600, T-2328, TA-5538, TAK-637, TKA-731, ZD-4974, ZD-6021, and pharmaceutically acceptable salts thereof. 
     
     
         10 . The method of  claim 8  or  9 , wherein the NK-1 antagonist is serlopitant or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The method of any one of  claims 8  to  10 , wherein the kappa-opioid receptor agonist is selected from asimadoline, bremazocine, butorphanol (a mu antagonist and kappa agonist), difelikefalin (CR845), dynorphin, enadoline, ketazocine, nalbuphine (a mu antagonist and kappa agonist), nalfurafine, salvinorin A, 2-methoxymethyl salvinorin B, 2-ethoxy methyl salvinorin B, 2-fluoroethoxymethyl salvinorin B, spiradoline, tifluadom, BRL-52537, FE 200665, GR-89696, HZ-2, ICI-199,441, ICI-204,448, LPK-26, SA-14867, U-50488, U-69,593, and pharmaceutically acceptable salts thereof. 
     
     
         12 . The method of  claim 11 , wherein the kappa-opioid receptor agonist is asimadoline, butorphanol, difelikefalin (CR845), nalbuphine or nalfurafine, or a pharmaceutically acceptable salt thereof. 
     
     
         13 . The method of any one of  claims 8  to  12 , wherein the pruritus is associated with dermatitis/eczema (e.g., atopic dermatitis), prurigo (e.g., porrigo nodularis), or a hepato-biliary disease (e.g., a cholestatic disorder such as cholestasis or primary biliary cirrhosis). 
     
     
         14 . The method of any one of  claims 8  to  13 , wherein the kappa-opioid receptor agonist is nalbuphine or a pharmaceutically acceptable salt thereof (e.g., Nalbuphine ER), and the pruritus is associated with prurigo (e.g., prurigo nodularis). 
     
     
         15 . A method of treating pruritus associated with dermatitis/eczema, psoriasis, prurigo, urticaria, cutaneous T-cell lymphoma (CTCL), epidermolysis bullosa, a burn or a hepato-biliary disease, comprising administering to a subject in need of treatment a therapeutically effective amount of a neurokinin-1 (NK-1) antagonist and a therapeutically effective amount of a mu-opioid receptor antagonist, wherein the NK-1 antagonist is not serlopitant. 
     
     
         16 . The method of  claim 15 , wherein the NK-1 antagonist is selected from aprepitant, fosaprepitant, befetupitant, casopitant, dapitant, ezlopitant, lanepitant, maropitant, netupitant, nolpitantium, orvepitant, rolapitant, tradipitant, vestipitant, vofopitant, hydroxyphenyl propamidobenzoic acid, maltooligosaccharides (e.g., maltotetraose and maltopentaose), spantides (e.g., spantide I and II), AV-608, AV-818, AZD-2624, BIT 1149 CL, CGP-4982:3, CJ-17493, CP-96345, CP-99994, CP-122721, DNK-333, FK-224, FK-888, GR-205171, GSK-424887, HSP-1.17, KRP-103, L-703606, L-733060, L-736281, L-759274, L-760735, LY-686017, M516102, MDL-105212, NKP-608, R-116031, R-116301, RP-67580, SCH-206272, SCH-388714, SCH-900978, SLV-317, SSR-240600, T-2328, TA-5538, TAK-637, TKA-731, ZD-4974, ZD-6021, and pharmaceutically acceptable salts thereof. 
     
     
         17 . The method of  claim 15  or  16 , wherein the mu-opioid receptor antagonist is selected from alvimopan, axelopran, bevenopran, butorphanol (a mu antagonist and kappa agonist), cyprodime, eptazocine, levallorphan (lorfan or naloxiphan), methylnaltrexone, naldemedine, nalmefene, nalbuphine (a mu antagonist and kappa agonist), nalodeine, nalorphine (lethidrone or nalline), naloxegol, naloxone, naloxol, naltrexone, 6β-naltrexol, samidorphan, SK-1405, and pharmaceutically acceptable salts thereof. 
     
     
         18 . The method of  claim 17 , wherein the mu-opioid receptor antagonist is butorphanol, nalmefene, naloxone, naltrexone or SK-1405, or a pharmaceutically acceptable salt thereof. 
     
     
         19 . The method of any one of  claims 15  to  18 , wherein the pruritus is associated with dermatitis/eczema (e.g., atopic dermatitis), prurigo (e.g., prurigo nodularis), CTCL (e.g., mycosis fungoides), a burn, or a hepato-biliary disease (e.g., a cholestatic disorder such as cholestasis or primary biliary cirrhosis). 
     
     
         20 . A method of treating pruritus associated with dermatitis/eczema, psoriasis, prurigo, urticaria, cutaneous T-cell lymphoma (CTCL), epidermolysis bullosa, a burn or a hepato-biliary disease, comprising administering to a subject in need of treatment a therapeutically effective amount of a neurokinin-1 (NK-1) antagonist and a therapeutically effective amount of an antidepressant, wherein the NK-1 antagonist is not serlopitant. 
     
     
         21 . The method of  claim 20 , wherein the NK-1 antagonist is selected from aprepitant, fosaprepitant, befetupitant, casopitant, dapitant, ezlopitant, lanepitant, maropitant, netupitant, nolpitantium, orvepitant, rolapitant, tradipitant, vestipitant, vofopitant, hydroxyphenyl propamidobenzoic acid, maltooligosaccharides (e.g., maltotetraose and maltopentaose), spantides (e.g., spantide 1 and 11), AV-608, AV-818, AZD-2624, HUE 1149 CL, CGP-49823, CJ-17493, CP-96345, CP-99994, CP-122721, DNK-333, FK-224, FK-888, GR-205171, GSK-424887, HSP-117, KRP-103, L-703606, L-733060, L-736281, L-759274, L-760735, LY-686017, M516102, MDL-105212, NKP-608, R-11.6031, R-116301, RP-67580, SCH-206272, SCH-388714, SCH-900978, SLV-317, SSR-240600, T-2328, TA-5538, TAK-637, TKA-731, ZD-4974, ZD-6021, and pharmaceutically acceptable salts thereof. 
     
     
         22 . The method of  claim 20  or  21 , wherein the antidepressant is selected from tricyclic antidepressants (e.g., amitriptyline, amitriptylinoxide, amoxapine, dosulepin [dothiepin], doxepin, cidoxepin and melitracen), tetracyclic antidepressants (e.g., amoxapine, maprotiline, mazindol, mianserin, mirtazapine, esmirtazapine and setiptiline), selective serotonin reuptake inhibitors (SSRIs, e.g., citalopram, dapoxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline), serotonin-norepinephrine reuptake inhibitors (SNRIs, e.g., bicifadine, doxepin, cidoxepin, duloxetine, milnacipran, levomilnacipran, sibutramine, venlafaxine, desvenlafaxine and SEP-227162), inhibitors of monoamine oxidases (e.g., selective MAO-A inhibitors [e.g., bifemelane, moclobemide, pirlindole {pirazidol} and toloxatone], selective MAO-B inhibitors [e.g., rasagiline and selegiline], and non-selective MAO-A/MAO-B inhibitors [e.g., hydracarbazine, isocarboxazid, nialamide, phenelzine and tranylcypromine]), and pharmaceutically acceptable salts and combinations thereof. 
     
     
         23 . The method of  claim 22 , wherein the antidepressant is or comprises amitriptyline, doxepin, cidoxepin, mirtazapine, esmirtazapine, fluvoxamine or paroxetine, or a pharmaceutically acceptable salt or any combination thereof. 
     
     
         24 . The method of any one of  claims 20  to  23 , wherein the pruritus is associated with dermatitis/eczema (e.g., atopic dermatitis), prurigo (e.g., prurigo nodularis), CTCL (e.g., mycosis fungoides), epidermolysis bullosa (e.g., epidermolysis bullosa simplex), or a hepato-biliary disease (e.g., a cholestatic disorder such as cholestasis or primary biliary cirrhosis). 
     
     
         25 . A method of treating pruritus associated with dermatitis/eczema, psoriasis, prurigo, urticaria, cutaneous T-cell lymphoma, epidermolysis bullosa, a burn or a hepato-biliary disease, comprising administering to a subject in need of treatment a therapeutically effective amount of a neurokinin-1 (NK-1) antagonist and a therapeutically effective amount of an inhibitor of a pro-inflammatory cytokine or a receptor therefor. 
     
     
         26 . The method of  claim 25 , wherein the NK-1 antagonist is selected from aprepitant, fosaprepitant, befetupitant, casopitant, dapitant, ezlopitant, lanepitant, maropitant, netupitant, nolpitantium, orvepitant, rolapitant, serlopitant, tradipitant, vestipitant, vofopitant, hydroxyphenyl propamidobenzoic acid, maltooligosaccharides (e.g., maltotetraose and maltopentaose), spantides (e.g., spantide I and II), AV-608, AV-818, AZD-2624, BIT 1149 CL, CGP-49823, CJ-17493, CP-96345, CP-99994, CP-122721, DNK-333, FK-224, FK-888, GR-205171, GSK-424887, HSP-117, KRP-103, L-703606, L-733060, L-736281, L-759274, L-760735, LY-686017, M516102, MDL-105212, NKP-608, R-116031, R-116301, RP-67580, SCH-206272, SCH-388714, SCH-900978, SLV-317, SSR-240600, T-2328, TA-5538, TAK-637, TKA-731, ZD-4974, ZD-6021, and pharmaceutically acceptable salts thereof. 
     
     
         27 . The method of  claim 25  or  26 , wherein the NK-1 antagonist is serlopitant or a pharmaceutically acceptable salt thereof. 
     
     
         28 . The method of any one of  claims 25  to  27 , wherein the inhibitor of a pro-inflammatory cytokine or a receptor therefor is selected from inhibitors of tumor necrosis factor-alpha (TNF-α) (e.g., adalimumab, certolizumab pegol, golimumab, infliximab, etanercept, bupropion and ART-620, inhibitors of interleukin-2 (IL-2) or receptor therefor (IL-2R) (e.g., basiliximab and daclizumab), inhibitors of IL-4 or IL-4R (e.g., dupilumab), inhibitors of IL-12 (e.g., briakinumab and ustekinumab) or IL-12R, inhibitors of IL-17 (e.g., ixekizumab and secukinumab) or IL-17R (e.g., brodalumab), inhibitors of IL-22 (e.g., fezakimimab) or IL-22R, inhibitors of IL-23 (e.g., briakinumab, guselkumab risankizumab, tildrakizumab [SCH-900222], ustekinumab and BI-6550661 or IL-23R, inhibitors of IL-31 or IL-31R (e.g., nernolizumab), and pharmaceutically acceptable salts and combinations thereof. 
     
     
         29 . The method of any one of  claims 25  to  28 , wherein the pruritus is associated with dermatitis/eczema (e.g., atopic dermatitis), psoriasis (e.g., plaque psoriasis), or prurigo (e.g., prurigo nodularis). 
     
     
         30 . The method of any one of  claims 25  to  29 , wherein the inhibitor of a pro-inflammatory cytokine or a receptor therefor is or comprises an inhibitor of IL-2 or IL-2R (e.g., basiliximab or daclizumab), an inhibitor of IL-4 or IL-4R (e.g., dupilumab), or an inhibitor of IL-31 or IL-31R (e.g., nemolizumab), or a pharmaceutically acceptable salt or any combination thereof, and the pruritus is associated with dermatitis/eczema (e.g., atopic dermatitis). 
     
     
         31 . The method of any one of  claims 25  to  29 , wherein the inhibitor of a pro-inflammatory cytokine or a receptor therefor is or comprises a TNF-α, inhibitor (e.g., adalimumab, certolizumab pegol, infliximab or etanercept), an inhibitor of IL-12 (e.g., ustekinumab) or IL-12R, an inhibitor of IL-17 (e.g., ixekizumab or secukinumab) or IL-17R (e.g., brodalumab), an inhibitor of IL-22 (e.g., fezakinumab) or IL-22R, or an inhibitor of IL-23 guselkumab, risankizumab, tildrakizumab or ustekinumab) or IL-23R, or a pharmaceutically acceptable salt or any combination thereof, and the pruritus is associated with psoriasis (e.g., plaque psoriasis). 
     
     
         32 . The method of any one of  claims 25  to  29 , wherein the inhibitor of a pro-inflammatory cytokine or a receptor therefor is or comprises an inhibitor of IL-31 or IL-31R (e.g., nemolizumab or a pharmaceutically acceptable salt thereof), and the pruritus is associated with prurigo (e.g., prurigo nodularis). 
     
     
         33 . A method of treating pruritus associated with dermatitis/eczema, psoriasis, prurigo, urticaria, cutaneous T-cell lymphoma, epidermolysis bullosa, a burn or a hepato-biliary disease, comprising administering to a subject in need of treatment a therapeutically effective amount of a neurokinin-1 (NK-1) antagonist and a therapeutically effective amount of a phosphodiesterase-4 (PDE4) inhibitor, wherein the NK-1 antagonist is not serlopitant for the treatment of pruritus associated with psoriasis. 
     
     
         34 . The method of  claim 33 , wherein the NK-1 antagonist is selected from aprepitant, fosaprepitant, befetupitant, casopitant, dapitant, ezlopitant, lanepitant, maropitant, netupitant, nolpitantium, orvepitant, rolapitant, serlopitant, tradipitant, vestipitant, vofopitant, hydroxyphenyl propamidohenzoic acid, maltooligosaccharides (e.g., maltotetraose and maltopentaose), spantides (e.g., spantide 1 and 11), AV-608, AV-818, AZD-2624, BITE 1149 CL, CGP-4982:3, CJ-17493, CP-96345, CP-99994, CP-122721, DNK-333, FK-224, FK-888, GR-205171, GSK-424887, HSP-117, KRP-103, L-703606, L-733060, L-736281, L-759274, L-760735, LY-686017, M516102, MDL-105212, NKP-608, R-116031, R-116301, RP-67580, SCH-206272, SCH-388714, SCH-900978, SLV-317, SSR-240600, T-2328, TA-5538, TAK-637, TKA-731, ZD-4974, ZD-6021, and pharmaceutically acceptable salts thereof. 
     
     
         35 . The method of  claim 33  or  34 , wherein the NK-1 antagonist is serlopitant or a pharmaceutically acceptable salt thereof. 
     
     
         36 . The method of any one of  claims 33  to  35 , wherein the PDE4 inhibitor is selected from apremilast, cilomilast, ibudilast, piclamilast, roflumilast, crisaborole, diazepam, luteolin, mesembrenone, rolipram, AN2728, E6005, and pharmaceutically acceptable salts thereof. 
     
     
         37 . The method of  claim 36 , wherein the PDE4 inhibitor is apremilast or crisaborole or a pharmaceutically acceptable salt thereof. 
     
     
         38 . The method of any one of  claims 33  to  37 , wherein the pruritus is associated with dermatitis/eczema (e.g., atopic dermatitis) or psoriasis g plaque psoriasis). 
     
     
         39 . The method of any one of  claims 33  to  38 , wherein the PDE4 inhibitor is apremilast or a pharmaceutically acceptable salt thereof, and the pruritus is associated with psoriasis (e.g., plaque psoriasis). 
     
     
         40 . A method of treating pruritus associated with a hepato-biliary disease, comprising administering to a subject in need of treatment a therapeutically effective amount of a neurokinin-1 (NK-1) antagonist and a therapeutically effective amount of a farnesoid X receptor (FXR) agonist. 
     
     
         41 . The method of  claim 40 , wherein the NK-1 antagonist is selected from aprepitant, fosaprepitant, befetupitant, casopitant, dapitant, ezlopitant, lanepitant, maropitant, netupitant, nolpitantium, orvepitant, rolapitant, serlopitant, tradipitant, vestipitant, vofopitant, hydroxyphenyl propamidohenzoic acid, maltooligosaccharides (e.g., maltotetraose and maltopentaose), spantides (e.g., spantide I and II) AV-608, AV-818, AZD-2624, BITE 1149 CL, CGP-49823, CJ-17493, CP-96345, CP-99994, CP-122721, DNK-333, FK-224, FK-888, GR-205171, GSK-424887, HSP-117, KRP-103, L-703606, L-733060, L-736281, L-759274, L-760735, LY-686017, M516102, MDL-105212, NKP-608, R-116031, R-116301, RP-67580, SCH-206272, SCH-388714, SCH-900978, SLV-317, SSR-240600, T-2328, TA-5538, TAK-637, TKA-731, ZD-4974, ZD-6021, and pharmaceutically acceptable salts thereof. 
     
     
         42 . The method of  claim 40  or  41 , wherein the NK-1 antagonist is serlopitant or a pharmaceutically acceptable salt thereof. 
     
     
         43 . The method of any one of  claims 40  to  42 , wherein FXR agonist is selected from cafestol, chenodeoxycholic acid, obeticholic acid, fexaramine, and pharmaceutically acceptable salts thereof. 
     
     
         44 . The method of  claim 43 , wherein the FXR agonist is obeticholic acid or a pharmaceutically acceptable salt thereof. 
     
     
         45 . The method of any one of  claims 40  to  44 , wherein the pruritus is associated with a cholestatic disorder (e.g., cholestasis or primary biliary cirrhosis [primary biliary cholangitis]). 
     
     
         46 . The method of  claim 45 , further comprising administering a cholesterol absorption-reducing or gallstone-dissolving agent (e.g., ursodeoxycholic acid [ursodiol] or chenodeoxycholic acid). 
     
     
         47 . A method of treating pruritus associated with dermatitis/eczema, psoriasis, prurigo, urticaria, cutaneous T-cell lymphoma (CTCL), epidermolysis bullosa, a burn or a hepato-biliary disease, comprising administering to a subject in need of treatment a therapeutically effective amount of a neurokinin-1 (NK-1) antagonist and a therapeutically effective amount of an additional therapeutic agent, wherein:
 the additional therapeutic agent is or comprises asimadoline, difelikefalin (CR845), nalbuphine, nalfurafine, SK-1405, 8-777469, LPL-389, CT327, apremilast, crisaborole, EBI-005, dupilumab, nemolizumab, NST-141 or SD-101, or a pharmaceutically acceptable salt or any combination thereof;   the NK-1 antagonist is not serlopitant for use in combination with CT327 to treat pruritus associated with atopic dermatitis, psoriasis or CTCL; and   the NK-1 antagonist is not serlopitant for use in combination with apremilast or crisahorole to treat pruritus associated with psoriasis.   
     
     
         48 . The method of  claim 47 , wherein the NK-1 antagonist is not serlopitant for use in combination with nalbuphine. 
     
     
         49 . The method of  claim 47 , wherein the NK-1 antagonist is not serlopitant for use in combination with SK-1405. 
     
     
         50 . The method of any one of  claims 47  to  49  wherein the NK-1 antagonist is selected from aprepitant, fosaprepitant, befetupitant, casopitant, dapitant, ezlopitant, lanepitant, maropitant, netupitant, nolpitantium, orvepitant, rolapitant, serlopitant, tradipitant, vestipitant, vofopitant, hydroxyphenyl propamidobenzoic acid, maltooligosaccharides (e.g., maltotetraose and maltopentaose), spantides (e.g., spantide I and II), AV-608, AV-818, ALD-2624, BIIF 1149 CL, CGP-49823, CJ-17493, CP-96345, CP-99994, CP-122721, DNK-333, FK-224, FK-888, GR-205171, GSK-424887, HSP-117, KRP-1103, L-703606, L-73:3060, L-736281, L-759274, L-760735, LY-686017, M516102, MDL-105212, NKP-608, R-116031, R-116301, RP-67580, SCH-206272, SCH-388714, SCH-900978, SLV-317, SSR-240600, T-2328, TA-5538, TAK-637, TKA-731, ZD-4974, ZD-6021, and pharmaceutically acceptable salts thereof. 
     
     
         51 . The method of  claim 50 , wherein the NK-1 antagonist is serlopitant or a pharmaceutically acceptable salt thereof. 
     
     
         52 . A method of preventing pruritus, comprising administering to a subject a therapeutically effective amount of a neurokinin-1 (NK-1) antagonist prior to development of pruritus. 
     
     
         53 . The method of  claim 52  wherein the NK-1 antagonist is selected from aprepitant, fosaprepitant, befetupitant, casopitant, dapitant, ezlopitant, lanepitant, maropitant, netupitant, nolpitantium, orvepitant, rolapitant, serlopitant, tradipitant, vestipitant, vofopitant, hydroxyphenyl propamidohenzoic acid, maltooligosaccharides (e.g., maltotetraose and maltopentaose), spantides (e.g., spantide I and II), AV-608, AV-818, AZD-2624, BIIF 1149 CL, CGP-49823, CJ-17493, CP-96345, CP-99994, CP-122721, DNK-333, FK-224, FK-888, GR-205171, GSK-424887, HSP-117, KRP-103, L-703606, L-733060, L-736281, L-759274, L-760735, LY-686017, M516102, MDL-105212, NKP-608, R-116031, R-116301, RP-67580, SCH-206272, SCH-388714, SCH-900978, SLV-317, SSR-240600, T-2328, TA-5538, TAK-637, TKA-731, ZD-4974, ZD-6021, and pharmaceutically acceptable salts thereof. 
     
     
         54 . The method of  claim 52  or  53 , wherein the NK-1 antagonist is serlopitant or a pharmaceutically acceptable salt thereof. 
     
     
         55 . The method of any one of  claims 52  to  54 , wherein the pruritus is acute pruritus. 
     
     
         56 . The method of any one of the preceding claims, further comprising administering one or more additional antipruritic or therapeutic agents.